RT Journal Article SR Electronic T1 Excitatory Postrhinal Projections to Principal Cells in the Medial Entorhinal Cortex JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 15860 OP 15874 DO 10.1523/JNEUROSCI.0653-15.2015 VO 35 IS 48 A1 Noriko Koganezawa A1 Ragnhild Gisetstad A1 Ellen Husby A1 Thanh P. Doan A1 Menno P. Witter YR 2015 UL http://www.jneurosci.org/content/35/48/15860.abstract AB The postrhinal cortex (POR) provides substantial input to the entorhinal cortex, mainly targeting superficial layers of the medial entorhinal cortex (MEC). Major inputs to POR originate in the visual and parietal cortex, thus providing neurons in MEC with a subset of cortical information relevant to their spatial firing properties. The POR takes a position that is comparable with that of the perirhinal cortex (PER) with regard to the lateral entorhinal cortex (LEC). Neurons in LEC and MEC show different functional properties likely reflecting differences in their respective inputs. Projections from PER to LEC exert a main inhibitory influence, which may relate to the sparse object-selective firing in LEC. In view of the continuous, spatially modulated firing properties of principal neurons in MEC, we tested in rats the hypothesis that projections from POR to MEC are functionally different from the PER-to-LEC counterpart in providing an excitatory drive to MEC. Our combined confocal and quantitative electron-microscopic observations indicated that POR projections target mainly principal cells in MEC, including neurons that project to the hippocampus. The ultrastructure of the majority of the synapses indicated that they are excitatory. Voltage-sensitive dye imaging in sagittal slices confirmed this morphologically derived conclusion, showing that the MEC network always responded with an overall depolarization, indicative for net excitatory transmission. In vitro single-cell recordings from principal cells showed only excitatory responses upon POR stimulation. These results show that POR provides an excitatory projection to MEC, differing fundamentally from the inhibitory projection of PER to LEC.SIGNIFICANCE STATEMENT The study provides anatomical and electrophysiological data indicating that projections from the postrhinal cortex to the medial entorhinal cortex (MEC) are excitatory, providing the substrate for high probability of information transfer and thus a continuous input stream into MEC. This is a relevant component of the spatial navigational network found in MEC. The findings are in contrast to previous reports on the parallel pathway from the perirhinal cortex to the lateral entorhinal cortex. This pathway, characterized by a preponderance of inhibitory connections, mediates information transfer with a low probability, likely related to the discontinuous object-related firing of neurons in the lateral entorhinal cortex.